Metabolic Correction of Primary Hemostasis in the Acute Phase of Traumatic Brain Injury

The aim of the study was to investigate the effect of ethylmethylhydroxypyridine on the ultrastructural alterations in endothelial cells of liver sinusoidal capillaries (SC) and primary hemostasis in the acute phase of traumatic brain injury (TBI).Materials and methods. Ultrastructural endothelial cell changes were studied in 36 female outbred rats in the acute phase of TBI using electron microscopy, and the platelet count was determined using a blood analyzer. The experimental group (n=18) animals received intraperitoneal injections of ethylmethylhydroxypyridine at the dose of 8.0 mg/kg per day for 12 days, and the control group (n=18) rats were administered with normal saline solution at the same dose.Results. Administration of ethylmethylhydroxypyridine in the early post TBI period reduced microvilli damage in endothelial, hepatic and stellate cells in the Disse space, whereas in the control group a significant decrease of these cells counts was detected. In contrast to the control group, the experimental group animals did not demonstrate thrombocytopenia on the days 1, 3, and 7 after injury. There was a significant increase in the platelet count compared with the baseline values, which was highest on day 12 after injury.Conclusion. Intraperitoneal administration of ethylmethylhydroxypyridine in rats in early post TBI period inhibited the TBI-associated damaging effect of secondary factors on liver sinusoid endothelial cells and platelet consumption

The Heavy Photon Search Test Detector

The Heavy Photon Search (HPS), an experiment to search for a hidden sector photon in fixed target electroproduction, is preparing for installation at the Thomas Jefferson National Accelerator Facility (JLab) in the Fall of 2014. As the first stage of this project, the HPS Test Run apparatus was constructed and operated in 2012 to demonstrate the experiment׳s technical feasibility and to confirm that the trigger rates and occupancies are as expected. This paper describes the HPS Test Run apparatus and readout electronics and its performance. In this setting, a heavy photon can be identified as a narrow peak in the e+ e− invariant mass spectrum above the trident background or as a narrow invariant mass peak with a decay vertex displaced from the production target, so charged particle tracking and vertexing are needed for its detection. In the HPS Test Run, charged particles are measured with a compact forward silicon microstrip tracker inside a dipole magnet. Electromagnetic showers are detected in a PbW04 crystal calorimeter situated behind the magnet, and are used to trigger the experiment and identify electrons and positrons. Both detectors are placed close to the beam line and split top-bottom. This arrangement provides sensitivity to low-mass heavy photons, allows clear passage of the unscattered beam, and avoids the spray of degraded electrons coming from the target. The discrimination between prompt and displaced e+ e− pairs requires the first layer of silicon sensors be placed only 10 cm downstream of the target. The expected signal is small, and the trident background huge, so the experiment requires very large statistics. Accordingly, the HPS Test Run utilizes high-rate readout and data acquisition electronics and a fast trigger to exploit the essentially 100% duty cycle of the CEBAF accelerator at JLab

Search for a Dark Photon in Electroproduced e + e − pairs with the Heavy Photon Search experiment at JLab

The Heavy Photon Search experiment took its first data in a 2015 engineering run using a 1.056 GeV, 50 nA electron beam provided by CEBAF at the Thomas Jefferson National Accelerator Facility, searching for a prompt, electroproduced dark photon with a mass between 19 and 81  MeV/c2. A search for a resonance in the e+e− invariant mass distribution, using 1.7 days (1170  nb−1) of data, showed no evidence of dark photon decays above the large QED background, confirming earlier searches and demonstrating the full functionality of the experiment. Upper limits on the square of the coupling of the dark photon to the standard model photon are set at the level of 6×10−6. Future runs with higher luminosity will explore new territory

Метаболическая коррекция сосудисто-тромбоцитарного звена системы гемостаза в остром периоде черепно-мозговой травмы у крыс

The aim of the study was to investigate the effect of ethylmethylhydroxypyridine on the ultrastructural alterations in endothelial cells of liver sinusoidal capillaries (SC) and primary hemostasis in the acute phase of traumatic brain injury (TBI).Materials and methods. Ultrastructural endothelial cell changes were studied in 36 female outbred rats in the acute phase of TBI using electron microscopy, and the platelet count was determined using a blood analyzer. The experimental group (n=18) animals received intraperitoneal injections of ethylmethylhydroxypyridine at the dose of 8.0 mg/kg per day for 12 days, and the control group (n=18) rats were administered with normal saline solution at the same dose.Results. Administration of ethylmethylhydroxypyridine in the early post TBI period reduced microvilli damage in endothelial, hepatic and stellate cells in the Disse space, whereas in the control group a significant decrease of these cells counts was detected. In contrast to the control group, the experimental group animals did not demonstrate thrombocytopenia on the days 1, 3, and 7 after injury. There was a significant increase in the platelet count compared with the baseline values, which was highest on day 12 after injury.Conclusion. Intraperitoneal administration of ethylmethylhydroxypyridine in rats in early post TBI period inhibited the TBI-associated damaging effect of secondary factors on liver sinusoid endothelial cells and platelet consumption.Цель исследования — изучить влияние этилметилгидроксипиридина на ультраструктурные изменения эндотелиоцитов синусоидных капилляров (СК) печени и сосудисто-тромбоцитарное звено системы гемостаза в остром периоде черепно-мозговой травмы (ЧМТ).Материалы и методы. В посттравматическом периоде (ПТП) ЧМТ на 36 аутбредных крысах-самках исследовали динамику изменения ультраструктуры эндотелиоцитов СК печени методом электронной микроскопии и определяли количество тромбоцитов на гемоанализаторе. В течение 12 сут. в опытной группе (n=18) животным внутрибрюшинно вводили этилметилгидроксипиридин в дозе 8,0 мг/кг массы тела в сутки, а в контрольной группе (n=18) — физиологический раствор натрия хлорида в том же объеме.Результаты. Введение этилметилгидроксипиридина в ПТП уменьшало повреждение микроворсинок эндотелиоцитов, гепатоцитов и звездчатых ретикулоэндотелиоцитов в пространстве Диссе, тогда как в контрольной группе в этот период обнаруживали их выраженную редукцию. В отличие от контрольной группы, у животных опытной группы не выявили тромбоцитопению в 1-, 3- и 7-е сутки после травмы, отметили статистически значимое увеличение числа тромбоцитов, относительно исходных данных, достигшее наибольшей величины к 12-м суткам после травмы.Заключение. Внутрибрюшинное введение этилметилгидроксипиридина крысам в раннем ПТП сдерживало повреждающее действие формирующихся после ЧМТ вторичных факторов на эндотелиоциты синусоидов печени и потребление тромбоцитов

Meglumine Sodium Succinate to Correct COVID-19-Associated Coagulopathy: the Feasibility Study

Aim of the study: to evaluate the effect of meglumine sodium succinate (MSS) on the efficacy of anticoagulant therapy in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.Materials and methods. Overall efficacy of treatment was analyzed in 12 patients hospitalized to ICU with the diagnosis of severe confirmed COVID-19 coronavirus infection (U07.1) complicated by bilateral multisegmental pneumonia. All patients received prophylactic anticoagulation with unfractionated heparin. The patients were divided into two groups: 7 of them received a multi-electrolyte solution containing MSS 5 ml/kg daily for the entire ICU stay (3-10 days) as a part of therapy; 5 patients received a similar volume of a conventional multi-electrolyte solution containing no metabolically active substrates and comprised a control group. Coagulation parameters were measured in arterial and venous blood of all patients at the following stages: 1) upon admission to the ICU; 2) 2-4 hours after the first dose of heparin; 3) 8-12 hours after the second dose of heparin; 4) 24 hours after the beginning of intensive therapy. On the 28th day of follow-up, mortality, duration of ICU stay, and incidence of thrombotic complications in the groups were evaluated. Nonparametric methods of statistical analysis were used to assess intragroup changes and intergroup differences.Results. The group of patients administered with MSS had significantly fewer thromboembolic events during 28 days of treatment and shorter ICU stay. These patients responded faster to anticoagulant therapy, which was suggested by more distinct changes in coagulation parameters, i.e. increased APTT, persisting viable thrombocyte population, reduced D-dimer and fibrinogen levels.Conclusion. The metabolic action of succinate possibly increases endothelial resistance to damaging factors and reduces its procoagulant activity. The hypothesis requires testing in a larger clinical study with a design including laboratory evaluation of the efficacy of varying doses of the studied drug as well as aiming at elucidation of the mechanisms of its effect on specific pro- and anticoagulation system components

Предупреждение нарушений барьерной функции кишечника при острой массивной кровопотере (экспериментальное исследование)

Purpose of the study: to investigate the influence of hypovolemia correction by infusion of malate-containing preparations and subsequent glutamine-enriched nutritional support on the maintenance of gut barrier and overhydration in animals with acute massive blood loss/  Materials and methods. Blood samples were harvested from the tail and portal veins of rats (n=100) at different time points after the acute blood loss (>30% V/V) . Bacterial blood cultures for growth, lipopolysaccharide and presepsin concentrations, colon structures and animal weight were analyzed in blood and plasma specimens 1 hour, one day and 3 days after the hypovolemia correction. To correct the hypovolemia, in the 1st series of experiments, the Ringer’s solution and standard nutrient mixture were used; in the 2nd series malatecontaining solution and standard nutrient mixture were administered; in the 3rd series a malate-containing solution and glutamine-enriched nutrient mixture were employed.Results. In the portal vein blood of intact animals, endotoxin measurement was equal to 17.8Ѓ}3.9 pg/ml, that of presepsin — 405.6Ѓ}80.1 pg/ml. At all stages, tail and portal blood bacterial cultures were negative demonstrating an absence of bacterial growth and gut barrier intactness for live microorganisms. One hour after hypovolemia correction and blood reinfusion, multifold increase in endotoxin concentration in the blood from both portal and tail veins was accompanied by significant increase of presepsin concentration. 24 hours after the blood loss, in the animals of the 2nd and 3rd series, the levels of endotoxin, presepsin, and edema of the colon mucous membrane and submucosal space has become lower than those in the 1st series. Three days later, the advantages of glutamine-containing nutrition in the 3rd series of the experiment were determined that revealed decreasing the endotoxin and presepsin concentrations in the portal and tail vein blood and diminishing the levels of interstitial edema of colon and animal weight growth.Conclusion. Administration of malate-containing infusion preparations and glutamine-enriched nutrition after an acute massive blood loss contributes to decreasing presepsin production in GIT organs, abrogating endotoxin translocation into the portal vein and systemic circulation, lessening severity of edema of the mucous membrane and submucosal space of the colon, and reducing the previously increased animal body mass.Цель исследования: изучить влияние инфузионной коррекции гиповолемии малатсодержащими препаратами и последующей глутаминобогащенной нутритивной поддержки на поддержание барьерной функции кишечника и гипергидратацию у животных с острой массивной кровопотерей.Материалы и методы. У 100 крыс после острой кровопотери (30% ОЦК) провели бактериальные «посевы» крови, исследование липополисахарида и пресепсина в крови хвостовой и воротной вен, структуры толстой кишки и веса животных через 1 час, сутки и 3 суток после восполнения гиповолемии. В 1-й серии применяли раствор Рингера и стандартную питательная смесь, во 2-й серии — малатсодержащий раствор и стандартную питательная смесь, в 3-й серии — малатсодержащий рас-твор и глутаминобогащенную питательную смесь.Результаты. У интактных животных в крови воротной вены значения эндотоксина составляли 17,8Ѓ}3,9 пг/мл, пресепсина — 405,6Ѓ}80,1 пг/мл. «Посевы» крови из хвостовой и воротной вен на всех эта-пах показали отсутствие бактериального роста, что подтверждает сохранение кишечного барьера для живых микроорганизмов. Через 1 час после восполнения гиповолемии и реинфузии крови отмечали многократный рост эндотоксина в крови воротной и хвостовой вены с достоверным увеличением уровня пресепсина. Через сутки после кровопотери во 2-й и 3-й сериях животных значения эндотоксина, пресепсина, отека слизистой оболочки и подслизистого пространства толстой кишки были меньше, чем в 1-й серии. Через 3 суток определили преимущества глутаминсодержащего питания в 3-й серии эксперимента: сдерживание нарастания эндотоксина и пресепсина в крови воротной и хвостовой вены, интерстициального отека толстой кишки, увеличения веса животного.Заключение. Применение малатсодержащих инфузионных препаратов и глутаминобогащенного питания после острой массивной кровопотери способствует снижению выработки пресепсина в органах желудочно-кишечного тракта, транслокации эндотоксина в воротную вену и системный кровоток, уменьшению степени выраженности отека слизистой оболочки, подслизистого пространства толстой кишки и нарастания веса животных

Влияние этилметилгидроксипиридина сукцината на динамику паттернов мозгового кровотока у пострадавших в остром периоде сочетанной черепномозговой травмы

The purpose of the investigation was to study the effect of the ethylmethylhydroxypyridine succinate (EMHPS) infusion on the dynamics of cerebral blood flow patterns in patients during the acute phase of severe concomitant traumatic brain injury. Materials and methods. The study involved two groups of patients, each of 25 persons aged 41.5 (29; 51) years on average, with a severe concomitant traumatic brain injury. The patients of the 1st (control) group were cured with a standard intensive care while in the 2nd (study) group the EMHPS infusion was added to the said standard treatment in a dose of 100 mg per hour through an infusion pump within 10 days. By transcranial dopplerography (TDG) testing the following cerebral macrocirculation parameters (CMP) were studied: systolic blood flow velocity (Vmax), diastolic blood flow velocity (Vmin), pulsation index (PI) and resistance index (RI). Results. The most frequent type of the cerebral blood flow (CBF) disorder noted in the both groups during the initial examination was a hindered perfusion pattern noticed in 15 and 16 patients from 1st and 2nd groups, respectively. Mild vasospasm was recorded in four patients in the 1st group and in three cases in the 2nd group. Signs of gross vasospasm were noted in two patients from each group. In two patients of each group patterns of hypoperfusion and hyperperfusion were noted. In the patients of the 1st group the CMP normalization was observed in six cases on the third day, in eight cases on the fifth day, in 12 cases on the seventh day, in 18 cases on the 10th day, while in the patients of the 2nd group the CMP normalization was observed on the 3rd day in 12 cases, on the 5th day in 15 cases, on the 7th day in 16 cases and on the 10th day in 20 cases. Conclusion. The most common patterns identified during the initial examination included hindered perfusion and vasospasm, which were transformed into a normoperfusion pattern through the hyperperfusion stage (reactive hyperemia). The EMHPS infusion in a dose of 100 mg per hour usually aids to normalize parameters within 3—5 days.Цель исследования: изучить влияние инфузии этилетилгидроксипиридинасукцината (ЭМГПС) на динамику паттернов мозгового кровотока у пострадавших в остром периоде тяжелой сочетанной черепно-мозговой травмы. Материалы и методы исследования. Обследовали 2 группы больных по 25 человек в каждой с тяжелой сочетанной ЧМТ. Средний возраст составил 41,5 (29; 51) лет. Больным в 1-й группе (контрольной) проводили стандартную интенсивную терапию, а во 2-й группе (исследуемой) дополнительно к стандартному лечению проводили инфузию ЭМГПС в дозе 100 мг/час через инфузомат на протяжении 10 суток. Методикой транскраниальной допплерографии (ТДГ) изучали показатели церебральной макроциркуляции (ПЦМ): систолическую скорость кровотока (Vmax), диастолическую скорость кровотока (Vmin), пульсационный индекс (PI) и индекс сопротивления (RI). Результаты исследования. В обеих группах наиболее частым видом нарушения мозгового кровотока (МК) при первичном исследовании был паттерн затрудненной перфузии: 15 и 16 случаев в 1-й и 2-й группах, соответственно. В 1-й группе в 4, а во 2-й в 3 случаях отмечали наличие мягкого ангиоспазма, а в 2 случаях в каждой группе отмечали признаки грубого ангиоспазма. У 2 больных в каждой группе отмечали паттерны гипоперфузии и гиперперфузии. У пациентов в 1-й группе на 3-е сутки исследования нормализация ПЦМ наблюдалась в 6, на 5-е сутки — в 8, на 7-е сутки — в 12, на 10 сутки — в 18 случаев, в то время, как у пациентов во 2-й группе на 3-е сутки нормализация ПЦМ наблюдалась в 12, на 5-е сутки — в 15, на 7-е сутки — в 16, на 10-е сутки — в 20 случаях. Заключение. Чаще всего при первичном обследовании выявлялись паттерны затрудненной перфузии и ангиоспазма, которые трансформировались в паттерн нормоперфузии через стадию гиперперфузии (реактивной гиперемии). Инфузия ЭМГПС в дозе 100 мг в час способствует нормализации параметров ПЦМ уже к 3—5 суткам

Large-angle production of charged pions by 3 GeV/c - 12.9 GeV/c protons on beryllium, aluminium and lead targets

Measurements of the double-differential $\pi^{\pm}$ production cross-section in the range of momentum 100 \MeVc \leq p < 800 \MeVc and angle 0.35 \rad \leq \theta < 2.15 \rad in proton--beryllium, proton--aluminium and proton--lead collisions are presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \GeVc to 12.9 \GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident particles were identified by an elaborate system of beam detectors. Results are obtained for the double-differential cross-sections at six incident proton beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc, 8.9 \GeVc (Be only), 12 \GeVc and 12.9 \GeVc (Al only)) and compared to previously available data

ВОЗМОЖНОСТИ ТЕРАПИИ ГЕМОРРАГИЧЕСКОГО ШОКА У БОЛЬНЫХ С ЖЕЛУДОЧНО-КИШЕЧНЫМ КРОВОТЕЧЕНИЕМ

Objective: to evaluate the antihypoxic effect of Mexicor in patients with gastrointestinal bleeding of ulcerative etiology. Materials and methods. The paper presents the materials obtained during the treatment of 53 patients with nonvaricose gastrointestinal bleeding who were hospitalized with grades II—III hemorrhagic shock. Results. Incorporation of Mexicor into the comprehensive program for the intensive therapy of acute gastrointestinal bleeding was ascertained to reduce the activity of prooxidant processes, and the manifestations of tissue hypoxia and systemic inflammation and to improve systemic hemodynamic parameters and the clinical course of an early posthemorrhagic period. Conclusion. The use of Mexicor in patients with gastric bleeding reduces the number of complications and the duration of treatment in the intensive care unit.  Цель исследования — оценить противогипоксическое и антиоксидантное действие Мексикора у больных с желудочно-кишечными кровотечениями язвенной этиологии. Материалы и методы. В статье представлены материалы, полученные в процессе лечения 53 больных язвенной болезнью с неварикозными желудочно-кишечными кровотечениями, госпитализированными в состоянии геморрагического шока II—III ст. Результаты. Установлено, что включение Мексикора в комплексную программу интенсивной терапии острых желудочно-кишечных кровотечений снижает в организме больных активность прооксидантных процессов, выраженность проявлений тканевой гипоксии и системного воспаления, улучшает показатели системной гемодинамики и клиническое течение раннего постгеморрагического периода. Заключение. Применение Мексикора у пациентов с желудочными кровотечениями снижает число осложнений, сокращает длительность лечения больных в отделении реанимации.

Searching for Prompt and Long-Lived Dark Photons in Electroproduced e⁺ e⁻ Pairs with the Heavy Photon Search Experiment at JLab

The heavy photon search experiment (HPS) at the Thomas Jefferson National Accelerator Facility searches for electroproduced dark photons. We report results from the 2016 engineering run consisting of 10 608  nb−1 of data for both the prompt and displaced vertex searches. A search for a prompt resonance in the e+e− invariant mass distribution between 39 and 179 MeV showed no evidence of dark photons above the large QED background, limiting the coupling of ε2≳10−5, in agreement with previous searches. The search for displaced vertices showed no evidence of excess signal over background in the masses between 60 and 150 MeV, but had insufficient luminosity to limit canonical heavy photon production. This is the first displaced vertex search result published by HPS. HPS has taken high-luminosity data runs in 2019 and 2021 that will explore new dark photon phase space